Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697918 | SCV000826552 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1804 of the AGRN protein (p.Val1804Met). This variant is present in population databases (rs754158999, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 575642). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000697918 | SCV002073012 | uncertain significance | Congenital myasthenic syndrome 8 | criteria provided, single submitter | clinical testing | The missense variant p.V1804M in AGRN (NM_198576.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to the ClinVar database as Uncertain Significance. The p.V1804M variant is observed in 7/26,066 (0.0269%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. In silico tools predict a damaging effect and the residue is not conserved across species. For these reasons, this variant has been classified as Uncertain Significance |